Etoposide (1) and Teniposide (2) are semisynthetic glucosidic cyclic acetals of podophyllotoxin (3) currently used in the chemotherapy for various types of cancer (Jardine. (1980) Anticancer Agents Based on Natural Products Models; Academic Press: New York, p. 319, Issell. (1982) Cancer Chemother. Pharmacol. 7:73). Another epipodophyllotoxin derivative, GL-331, has been developed and tested in phase II clinical trials against various cancers (Lee et al. (1995) Food and Drug Analysis. 3:209). Interestingly, although podophyllotoxin inhibits the assembly of microtubules, the primary action mode of its 4β-congeners, the epipodophyllotoxins, is to inhibit the catalytic activity of topoisomerase II by stabilizing the covalent topoisomerase II-DNA cleavable complex, cause DNA strands breaking and eventually lead to cell death (Osheroff et al. (1991) BioEssays 13:269, Alton & Harris (1993) Br. J. Haematol. 85:241-245, Cho et al. (1996) J. Med. Chem. 39:1383-1395, MacDonald et al. (1991) DNA Topoisomerase in Cancer; Oxford University Press: New York, p. 119).
U.S. Pat. No. 5,300,500 to Lee et al. describes a podophyllotoxin analog of formula 4-V as follows: 
There remains a need for new etoposide analogs with anticancer and antitumor activity.